Thiopyrano[2,3-e]indol-2-ones: angelicin heteroanalogues with potent photoantiproliferative activity.
A new class of compounds, the thiopyrano[2,3-e]indol-2-ones, bioisosters of the angular furocoumarin angelicin, was synthesized with the aim of obtaining new photochemotherapeutic agents. In particular 7,8-dimethyl-thiopyranoindolone 6c s showed a remarkable phototoxicity and a great dose UVA dependence reaching IC(50) values at submicromolar level. This latter photoinduced a massive apoptosis and a remarkable photodamage to lipids and proteins. Although it did not intercalate DNA, it was able to cause photooxidation of DNA bases.
Barraja
Paola
P
Dipartimento Farmacochimico, Tossicologico e Biologico Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
Diana
Patrizia
P
Montalbano
Alessandra
A
Carbone
Anna
A
Cirrincione
Girolamo
G
Viola
Giampietro
G
Salvador
Alessia
A
Vedaldi
Daniela
D
Dall'acqua
Francesco
F
D017209:Apoptosis; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D011564:Furocoumarins / Q000737:chemistry*; D018922:HL-60 Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D019169:Jurkat Cells; D015227:Lipid Peroxidation / Q000528:radiation effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D011564:Furocoumarins; D007211:Indoles; D017319:Photosensitizing Agents; D011506:Proteins; D004247:DNA; C011659:angelicin